Whipple's disease is a rare, generalized inflammatory disorder due to the recently described bacterium Tropheryma whippelii. We report an unusual, successfully treated case of a 32-year-old woman, who presented with a 25 month history of large abdominal lymphomas, polyserositis and cachexia. The diagnosis of Whipple's disease was confirmed by duodenoscopy, lymph node and duodenal histology and polymerase chain reaction analysis of biopsy material and cerebrospinal fluid. A prolonged convulsive seizure with a subsequent 5 day period of coma were interpreted as signs of cerebral involvement. Under antibiotic treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) the patient recovered completely, CT scans showed a complete regression of abdominal lymphomas. The therapy was continued over 18 months without the occurrence of a relapse.